Pd-Catalyzed Hydroxyl-Directed Cascade Hydroarylation/C-H Germylation of Nonterminal Alkenes and Aryl Iodides.

Pd-catalyzed cascade hydroarylation and C-H germylation of nonterminal alkenes and aryl iodides enabled by hydroxyl assistance have been developed. The key step in this C-H germylation cascade is the formation of a highly reactive oxo-palladacycle intermediate, which markedly restrained the ß-H elimination process. Mechanistically, control experiments indicated that the hydroxyl group played an important role in this process. This transformation shows excellent reactivity and selectivity for most substrates investigated.

Cost-effectiveness of medical migration for chronic kidney disease: a national cross-sectional study in China.

BACKGROUND: The phenomenon of medical migration is common in China. Due to the limited capacity and substantial geographical variation in medical practice, patients with chronic kidney disease (CKD) travel more frequently to seek medical care. We aimed to assess the cost-effectiveness of medical migration for CKD patients in China and provide real-world evidence for the allocation of CKD resources. METHODS: Records of patients with CKD between January 2014 and December 2018 were extracted from a large national database. A patient is defined as a medical migrant if she travelled across the provincial border to a non-residential province to be admitted for inpatient care. The propensity score matching method is used to estimate the effect of medical migration on medical expenditure, length of hospital stay, and in-hospital mortality. The cost-effectiveness is evaluated by comparing the estimated cost per life saved with contemporaneous estimates of the value of a statistical life. RESULTS: Among 4,392,650 hospitalizations with CKD, medical migrants accounted for 4.9% in 2018. Migrant patients were estimated to incur a 26.35% increase in total medical expenditure, experience a 0.24-percentage-points reduction in in-hospital mortality rates, and a 0.49-days reduction in length of hospital stay compared to non-migrant patients. Overall, medical migration among CKD patients incurred an average of 1 million yuan per life saved, which accounted for 20-40% of contemporaneous estimates of the value of a statistical life. Compared with migrant patients with self-payment and commercial insurance, migrant patients with public health insurance (urban basic medical insurance and new rural co-operative medical care) incurred lower cost per life saved. Cost per life saved for CKD patients was similar between female and male, lower among older population, and varied substantially across regions. CONCLUSIONS: The medical care seeking behaviors of CKD patients was prominent and medical resources of kidney care were unevenly allocated across regions. Medical migration led to a reduction in mortality, but was associated with higher medical expenditure. It is imperative to reduce the regional disparity of medical resources and improve the clinical capacity. Our study shows that it is imperative to prioritize resource allocation toward improving kidney health and regional health care planning.

Effects of ambient temperature on hospital admissions for obstructive nephropathy in Wuhan, China: A time-series analysis.

Under the background of global warming, it has been confirmed that heat exposure has a huge impact on human health. The current study aimed to evaluate the effects of daily mean ambient temperature on hospital admissions for obstructive nephropathy (ON) at the population level. A total of 19,494 hospitalization cases for ON in Wuhan, China from January 1, 2015 to December 31, 2018 were extracted from a nationwide inpatient database in tertiary hospitals according to the International Classification of Diseases (ICD)- 10 codes. Daily ambient meteorological and pollution data during the same period were also collected. A quasi-Poisson Generalized Linear Model (GLM) combined with a distributed lag non-linear model (DLNM) was applied to analyze the lag-exposure-response relationship between daily mean temperature and daily hospital admissions for ON. Results showed that there were significantly positive associations between the daily mean temperature and ON hospital admissions. Relative to the minimum-risk temperature (-3.4 â„ƒ), the risk of hospital admissions for ON at moderate hot temperature (25 â„ƒ, 75th percentile) occurred from lag day 4 and stayed to lag day 12 (cumulative relative risk [RR] was 1.846, 95 % confidence interval [CI]: 1.135-3.005, over lag 0-12 days). Moreover, the risk of extreme hot temperature (32 â„ƒ, 99th percentile) appeared immediately and lasted for 8 days (RR = 2.019, 95 % CI: 1.308-3.118, over lag 0-8 days). Subgroup analyses indicated that the middle-aged and elderly (≥45 years) patients might be more susceptible to the negative effects of high temperature, especially at moderate hot conditions. Our findings suggest that temperature may have a significant impact on the acute progression and onset of ON. Higher temperature is associated with increased risks of hospital admissions for ON, which indicates that early interventions should be taken in geographical settings with relatively high temperatures, particularly for the middle-aged and elderly.

Secondary Phosphine Sulfide-Enabled Iridium-Catalyzed Asymmetric Allylic Substitution.

An iridium-catalyzed asymmetric synthesis of branched allylic phosphine compounds under mild conditions is reported. Products bearing various functional groups can be synthesized with excellent stereoselectivity (up to 99.9 % ee) and regioselectivity. The employment of phosphine sulfides with relatively low deactivation capacity against metal catalysts is crucial for the success of this reaction.

Association between pulse pressure, systolic blood pressure and the risk of rapid decline of kidney function among general population without hypertension: results from the China health and retirement longitudinal study (CHARLS).

BACKGROUND: Association between blood pressure (BP) and kidney function among the middle and old aged general population without hypertension remains unclear. METHODS: Participants aged ≥ 45 years, with complete data in 2011 and 2015 interviews of the China Health and Retirement Longitudinal Study(CHARLS), and without pre-existing hypertension were included. Systolic BP (SBP) was categorized as low (< 120 mmHg), medium (120-129 mmHg), and high (120-139 mmHg). Diastolic BP (DBP) was categorized as low (< 60 mmHg), medium (60-74 mmHg), and high (75-89 mmHg). Pulse pressure (PP) was categorized as normal (< 60 mmHg) and high (≥ 60 mmHg). The outcome was defined as rapid decline of estimated glomerular filtration rate(eGFR, decline ≥ 4 ml/min/1.73 m2/year). BP combination was designed according to the category of SBP and PP. The association between BP components, types of BP combination, and the risk of rapid decline of eGFR was analyzed using multivariate logistic regression models, respectively. Age-stratified analyses were conducted. RESULTS: Of 4,534 participants included, 695(15.3%) individuals were recognized as having rapid decline of eGFR. High PP[odds ratio(OR) = 1.34, 95%confidence interval(CI) 1.02-1.75], low SBP (OR = 1.28, 95%CI 1.03-1.59), and high SBP (OR = 1.32, 95% CI 1.02-1.71) were significantly associated with the risk of eGFR decline. Low SBP were associated with 65% increment of the risk of eGFR decline among participants aged < 55 years. The combination of high SBP and high PP (OR = 1.79, 95% CI 1.27-2.54) and the combination of low SBP and high PP (OR = 3.07, 95% CI 1.24-7.58) were associated with the increased risk of eGFR decline among the middle and old aged general population. CONCLUSION: Single and combination of high PP and high SBP could be the risk indicators of eGFR decline among the middle and old aged general population.

Estimation of Prevalence of Kidney Disease Treated With Dialysis in China: A Study of Insurance Claims Data.

RATIONALE & OBJECTIVE: The national prevalence of dialysis in China has not been well studied. We aimed to estimate the prevalence of kidney disease treated with dialysis and predict the trend using claims data in order to provide evidence for developing prevention strategies. STUDY DESIGN: Cross-sectional study of insurance claims. SETTING & PARTICIPANTS: Medical claims data from January 1, 2013, to December 31, 2017, were extracted from a large claims database by using a 2-stage sampling design to obtain a national sample covered by the urban basic medical insurance, the most predominant insurance program in China. EXPOSURE: Patients receiving maintenance dialysis, including hemodialysis (HD) and peritoneal dialysis (PD), were identified according to medical billing data and International Classification of Diseases, Tenth Revision (ICD-10) codes. OUTCOMES: The age- and sex-standardized population prevalence of kidney disease treated with dialysis was estimated by year and treatment modality. ANALYTICAL APPROACH: Crude and age- and sex-standardized prevalence of kidney disease treated with dialysis were calculated stratified by year and treatment modality. The gray Verhulst model was used to predict dialysis prevalence from 2018 to 2025. RESULTS: The age-and sex-standardized prevalence of dialysis patients increased from 255.11 per million population (pmp) in 2013 to 419.39 pmp in 2017. The age- and sex-standardized prevalence of HD and PD in 2017 were 384.41 pmp and 34.98 pmp, respectively, and the total number of dialysis patients in China was estimated to be 581,273. The prevalence of dialysis was predicted to rise above 2017 levels, with a predicted prevalence of 534.60 pmp in 2020 and 629.67 pmp in 2025, corresponding to 744,817 and 874,373 patients, respectively. LIMITATIONS: Claims data have potential errors in classification of patients, and population selection bias may have limited inferences to the entire Chinese population. CONCLUSIONS: The prevalence of kidney disease treated with dialysis has risen between 2013 and 2017 in China and is predicted to increase further through 2025. These findings highlight the importance of prevention and control strategies to reduce the escalating burden of kidney failure.

Cobalt-Catalysed Asymmetric Addition and Alkylation of Secondary Phosphine Oxides for the Synthesis of P-Stereogenic Compounds.

The catalytic asymmetric synthesis of P-chiral phosphorus compounds is an important way to construct P-chiral ligands. Herein, we report a new strategy that adopts the pyridinyl moiety as the coordinating group in the cobalt-catalysed asymmetric nucleophilic addition/alkylation of secondary phosphine oxides. A series of tertiary phosphine oxides were generated with up to 99 % yield and 99.5 % ee, and with broad functional-group tolerance. Mechanistic studies reveal that (R)-secondary phosphine oxides preferentially interact with the cobalt catalysts to produce P-stereogenic compounds.

Executive summary for China Kidney Disease Network (CK-NET) 2016 Annual Data Report.

Chronic kidney disease (CKD) has been recognized as a public health problem globally. The spectrum of CKD in China has been evolving toward that of developed countries, which will have enormous impacts on the health care system. However, there has been no well-established national surveillance system for kidney diseases. Furthermore, China still faces several challenges of kidney care, including limited capacity and efficiency, suboptimal awareness, and huge heterogeneity in diagnosis and treatment. The China Kidney Disease Network has published 2 reports regarding the burden of CKD and end-stage kidney disease in China and intends to become a comprehensive surveillance system for kidney diseases based on multisource data. With the expansion of research group and data sources, the content of the China Kidney Disease Network 2016 Annual Data Report was further enriched. Section I addresses the epidemiologic characteristics of patients with CKD based on a national inpatient database, Hospital Quality Monitoring System, covering more than 52% of China's tertiary hospitals in China in 2016. Section II focuses on the burden of patients receiving dialysis, mainly based on the nationwide claims database, China Health Insurance Research Association database, which collects data from approximately 2% of the insured population from the municipalities/provincial capital cities and approximately 5% from the prefecture-level cities. An independent chapter regarding dialysis in 3 provincial dialysis quality control centers has been added. The China Kidney Disease Network 2016 Annual Data Report symbolizes a successful team effort in the era of big data, with support from the specialists and partners of the collaborative network, which is of substantial value for understanding the burden of kidney diseases in China and developing prevention and control strategies.

Early versus late acute kidney injury among patients with COVID-19-a multicenter study from Wuhan, China.

BACKGROUND: Acute kidney injury (AKI) is an important complication of coronavirus disease 2019 (COVID-19), which could be caused by both systematic responses from multi-organ dysfunction and direct virus infection. While advanced evidence is needed regarding its clinical features and mechanisms. We aimed to describe two phenotypes of AKI as well as their risk factors and the association with mortality. METHODS: Consecutive hospitalized patients with COVID-19 in tertiary hospitals in Wuhan, China from 1 January 2020 to 23 March 2020 were included. Patients with AKI were classified as AKI-early and AKI-late according to the sequence of organ dysfunction (kidney as the first dysfunctional organ or not). Demographic and clinical features were compared between two AKI groups. Their risk factors and the associations with in-hospital mortality were analyzed. RESULTS: A total of 4020 cases with laboratory-confirmed COVID-19 were included and 285 (7.09%) of them were identified as AKI. Compared with patients with AKI-early, patients with AKI-late had significantly higher levels of systemic inflammatory markers. Both AKIs were associated with an increased risk of in-hospital mortality, with similar fully adjusted hazard ratios of 2.46 [95% confidence interval (CI) 1.35-4.49] for AKI-early and 3.09 (95% CI 2.17-4.40) for AKI-late. Only hypertension was independently associated with the risk of AKI-early. While age, history of chronic kidney disease and the levels of inflammatory biomarkers were associated with the risk of AKI-late. CONCLUSIONS: AKI among patients with COVID-19 has two clinical phenotypes, which could be due to different mechanisms. Considering the increased risk for mortality for both phenotypes, monitoring for AKI should be emphasized during COVID-19.

Comparative analysis of CpG islands in equine infectious anemia virus strains.

Increasing evidence suggests that DNA methylation has key roles in the replication of retroviruses, including lentiviruses, and pathogenesis of diseases. However, the precise characteristics of CpG islands are not known for many retroviruses. In this study, we compared the distribution of CpG islands among strains of equine infectious anemia virus (EIAV), a lentivirus in the family Retroviridae and a model for HIV research. We identified CpG islands in 32 full-length EIAV genomic sequences obtained from the GenBank database using MethPrimer. Only one CpG island, from 100 to 120 bp, was identified in the genomes of EIAV strains DV10, DLV3-A, and DLV5-10 from China, V26 and V70 from Japan, and IRE H3, IRE F2, IRE F3, and IRE F4 from Ireland. Importantly, the CpG island was located within the Rev gene, which is required for the expression of viral cis-acting elements and the production of new virions. These results suggest that the distribution, length, and genetic properties of CpG islands differ among EIAV strains. Future research should focus on the biological significance of this CpG island within rev to improve our understanding of the precise roles of CpG islands in epigenetic regulation in the species.

Pseudo-Yang-Lee Edge Singularity Critical Behavior in a Non-Hermitian Ising Model.

The quantum phase transition of a one-dimensional transverse field Ising model in an imaginary longitudinal field is studied. A new order parameter M is introduced to describe the critical behaviors in the Yang-Lee edge singularity (YLES). The M does not diverge at the YLES point, a behavior different from other usual parameters. We term this unusual critical behavior around YLES as the pseudo-YLES. To investigate the static and driven dynamics of M, the (1+1) dimensional ferromagnetic-paramagnetic phase transition ((1+1) D FPPT) critical region, (0+1) D YLES critical region and the (1+1) D YLES critical region of the model are selected. Our numerical study shows that the (1+1) D FPPT scaling theory, the (0+1) D YLES scaling theory and (1+1) D YLES scaling theory are applicable to describe the critical behaviors of M, demonstrating that M could be a good indicator to detect the phase transition around YLES. Since M has finite value around YLES, it is expected that M could be quantitatively measured in experiments.

Risk HLA class II alleles and amino acid residues in myeloperoxidase-ANCA-associated vasculitis.

A genome-wide association study (GWAS) indicated that myeloperoxidase-ANCA associated vasculitis (AAV) is associated with HLA-DQ. However, susceptibility alleles in these loci have been under-investigated. Here we genotyped 258 Chinese patients with myeloperoxidase-AAV and 597 healthy control individuals at HLA DRB1, DQA1, DQB1 and DPB1, and extracted the encoded amino acid sequences from the IMGT/HLA database. The replication cohort included 97 cases and 107 controls. T cell epitopes of myeloperoxidase were predicted and docked to the HLA molecules. We found DQA1∗0302 (odds ratio 2.34 (95% confidence interval 1.75-3.14)) and DQB1∗0303 (odds ratio 1.89 (1.45-2.48)) were risk alleles for myeloperoxidase-AAV. They are in overt linkage disequilibrium (r2 0.69) and the haplotype DQA1∗0302-DQB1∗0303 presents a significant risk (haplotype score 6.39) as well. Aspartate160 on the DQ α chain (odds ratio 2.06 (1.60-2.67)), encoded by DQA1∗0302, and isoleucine185 on the DQ ß chain (odds ratio 1.73 (1.38-2.18)), encoded by DQB1∗0303, both located in the α2ß2 domains, conferred significant risk for myeloperoxidase-AAV. Homologous modeling showed that DQα∗160D may confer susceptibility to myeloperoxidase-AAV by altering dimerization of the HLA molecules. Thus, more attention should be paid to the roles of amino acids in the α2ß2 domains in addition to the α1ß1 binding groove of HLA class II molecules.

HLA class II alleles differing by a single amino acid associate with clinical phenotype and outcome in patients with primary membranous nephropathy.

Genome-wide associations and HLA genotyping have revealed associations between HLA alleles and susceptibility to primary membranous nephropathy. However, associations with clinical phenotypes and kidney outcome are poorly defined. We previously identified DRB1*1501 and DRB1*0301 as independent risk alleles for primary membranous nephropathy. Here, we investigated HLA associations with demographic characteristics, anti-phospholipase A2 receptor (PLA2R) antibody, treatment response and kidney outcome after a median follow-up of 52 months in 258 patients. DRB1*0301, but not DRB1*1501, was associated with a significantly higher level of PLA2R antibody (odds ratio 1.58, 95% confidence interval 1.13-2.22). Although DRB1*1502, which differs from DRB1*1501 by a single amino acid, was not a risk allele for primary membranous nephropathy (odds ratio 1.01), it was associated with significantly lower estimated glomerular filtration rates both at baseline (1.79, 1.18-2.72) and at last follow-up (1.72, 1.17-2.53), a significantly worse renal outcome by Kaplan-Meier analysis and a significantly higher risk of end-stage renal disease by Cox regression analysis (hazard ratio 4.52, 1.22-16.74). Nevertheless, the absence of remission remained the only independent risk factor for end-stage renal disease by multivariate analysis. DRB1*1502 was also associated with a significantly higher median PLA2R antibody level [161.4 vs. 36.3 U/mL] and showed interaction with DRB1*0301 for this variable. Thus, HLA genes control PLA2R antibody production and primary membranous nephropathy severity and outcome. Additionally, DRB1*1502 behaves like a modifier gene with a strong predictor value when associated with HLA risk alleles. Other modifier genes need further investigations in larger cohorts.

[Multiple effect of simvastatin on vascular endothelium of hypercholesterolemia patients].

OBJECTIVE: To observe the multiple influence of cholesterol-lowering drug (simvastatin) on ankle brachial index (ABI), flow-mediated dilation (FMD) and nitroglycerin-mediated dilation (NMD) of brachial artery blood vessel endothelium, and plasma level of monocyte chemotactic protein 1 (MCP-1) of hypercholesterolemia patients without coronary heart disease (CHD). METHODS: In the study, 51 patients with hypercholesterolemia application were treated with simvastatin (20 mg/d) therapy for 12 weeks. The metabolic index, ankle brachial index (ABI), FMD of brachial artery blood vessel endothelium detected by color doppler ultrasound instrument, the NMD of artery endothelial and the level of MCP 1 were measured before and after therapy respectively. All the results were analyzed and compared with another 30 cases of hypercholesterolemia patients selected without simvastatin treatment. RESULTS: After simvastatin therapy, the TC (total cholesterol) and LDL-C (low density lipoprotein cholesterin) levels were reduced apparently,the values decreased from the original (6.06 ± 1.03) mmol/L and (3.60 ± 0.82) mmol/L to (4.98 ± 1.34) mmol/L and (3.41 ± 0.10) mmol/L respectively (P<0.01, P< 0.05). Compared with no simvastatin treatment, the bilateral ABI levels were significantly elevated. The right side of ABI (ABIR) elevated from 1.11 ± 0.06 to 1.19 ± 0.07, and the left side of ABI (ABIL) also elevated from 1.12 ± 0.06 to 1.19 ± 0.10 (both sides were P<0.01). The FMD significantly increased from 7.75% ± 11.30% to 14.20% ± 15.39% (P < 0.05). The plasma levels of MCP-1 were apparently reduced from (112.0 ± 7.8) ng/L to (108.9 ± 6.2) ng/L (P < 0.05). All these items showed no obvious change within the control group. CONCLUSION: The API, FMD and plasma levels of MCP-1 of hypercholesterolemia patients without clear coronary heart disease can be improved by simvastatin treatment.

Blood pressure in the longevous population with different status of hypertension and frailty.

Blood pressure(BP) of the longevous population with hypertension and/or frailty was under-investigated. To investigate the association between age, BP, variation of BP, and survival among the old adults with different status of hypertension and frailty, the present study included adults ≥65 years in the Chinese Longitudinal Healthy Longevity Survey (2008-2018), defined frailty using the Fried criteria, and identified hypertension by self-report or SBP/DBP ≥ 140/90 mm Hg. The association between age and BP were investigated using linear regression models. Variation of BP was defined if annual change of BP lower than quartile 1(sharp decrease) or higher than quartile 3(sharp increase). The association between age and BP variation were investigated using multinominal logistic regression models. The association between BP and survival was analyzed using Cox regression models. Among 13,447 adults (centenarian: 1965[14.6%]), age was positively associated with SBP in robust hypertensive elderly but negatively associated with it in frail hypertensive elderly. Annual change of BP was more likely to be increment among the normotensive elderly, but be decrement among the hypertensive elderly, especially among those with frailty. SBP < 120 mmHg was the risk factor of mortality among the frail oldest-old (≥85 years) while SBP ≥ 150 mmHg was that among the robust young-old (65-84 years). DBP ≥ 90 mmHg was the risk factor of mortality both in the robust young-old and the frail oldest old. In conclusion, age and frailty might be the criteria to predict the change of BP to guide the BP management of the longevous population.

Socioeconomic support, quality of life, and prognosis of frailty among the older adults.

Background: Although socioeconomic support is recommended for frailty management, its association with the prognosis of frailty is unclear. Methods: Using data from participants aged ≥65 years in the Chinese Longitudinal Healthy Longevity Survey (2008-2018), the associations between socioeconomic support (source of income, medical insurance, community support, living status), onset of prefrailty/frailty, and worsening of prefrailty, were analyzed using multinominal logistic regression models. The associations between self-reported low quality of life (QoL) and reversion of prefrailty/frailty were analyzed using multivariate logistic regression models. Associations with mortality risk were analyzed using Cox proportional hazard regression models. Results: A total of 13,859 participants (mean age: 85.8 ± 11.1 years) containing 2056 centenarians were included. Financial dependence was a risk factor for low QoL among prefrail/frail individuals, but not among robust individuals. Having commercial or other insurance, and receiving social support from the community were protective factors for low QoL among prefrail/frail individuals and for the worsening of prefrailty. Continuing to work was a risk factor for low QoL, but a protective factor for worsening of prefrailty. A negative association between continuing to work and mortality existed in prefrail individuals aged <85 years and ≥85 years. Living alone was a risk factor for low QoL, but was not significantly associated with frailty prognosis. Conclusions: Prefrail and frail individuals were vulnerable to changes in socioeconomic support and more sensitive to it compared with robust individuals. Preferential policies regarding financial support, social support, and medical insurance should be developed for individuals with frailty.

Association between ambient PM1 and the prevalence of chronic kidney disease in China: A nationwide study.

Particulate of diameter ≤ 1 µm (PM1) presents a novel risk factor of adverse health effects. Nevertheless, the association of PM1 with the risk of chronic kidney disease (CKD) in the general population is not well understood, particularly in regions with high PM1 levels like China. Based on a nationwide representative survey involving 47,204 adults and multi-source ambient air pollution inversion data, the present study evaluated the association of PM1 with CKD prevalence in China. The two-year average PM1, particulate of diameter ≤ 2.5 µm (PM2.5), and PM1-2.5 values were accessed using a satellite-based random forest approach. CKD was defined as estimated glomerular filtration rate < 60 ml/min/1.73 m2 or albuminuria. The results suggested that a 10 µg/m3 rise in PM1 was related to a higher CKD risk (odds ratio [OR], 1.13; 95% confidence interval [CI] 1.08-1.18) and albuminuria (OR, 1.11; 95% CI, 1.05-1.17). The association between PM1 and CKD was more evident among urban populations, older adults, and those without comorbidities such as diabetes or hypertension. Every 1% increase in the PM1/PM2.5 ratio was related to the prevalence of CKD (OR, 1.03; 95% CI, 1.03-1.04), but no significant relationship was found for PM1-2.5. In conclusion, the present study demonstrated long-term exposure to PM1 was associated with an increased risk of CKD in the general population and PM1 might play a leading role in the observed relationship of PM2.5 with the risk of CKD. These findings provide crucial evidence for developing air pollution control strategies to reduce the burden of CKD.

Differences in CpG island distribution between exogenous and endogenous jaagsiekte sheep retrovirus strains.

The jaagsiekte sheep retrovirus (JSRV), belonging to the betaretrovirus genus of the retroviridae family, includes both exogenous and endogenous jaagsiekte sheep retroviruses (exJSRV and enJSRV, respectively). At the proviral genome level, exJSRV and enJSRV strains have a high degree of similarity with their main variation regions being the LTR, gag, and env genes. In this study, for the first time, we investigated and compared the distribution of CpG islands between these enJSRV and exJSRV strains. Specifically, we analyzed a total of 42 full-length JSRV genomic sequences obtained from the GenBank® database to identify CpG islands in the exJSRV and enJSRV genomes using the MethPrimer software. Our results showed that the CpG islands in the two JSRV strains were mainly distributed in the LTR, gag, and env genes. In exJSRVs, 66.66% (6/9), 33.33% (3/9), and 100% (9/9) of the sequences presented at least one CpG island in LTR, gag, env genes, respectively, and for enJSRVs, 84.84% (28/33), 57.57% (19/33), and 96.96% (32/33) of the sequences presented at least one CpG island in the LTR, gag, and env genes. These findings suggested that the distribution, length, and genetic traits of CpG islands were different for the exJSRV and enJSRV strains. In future, it would be necessary to demonstrate the biological significance of CpG islands within these genes in exJSRV and enJSRV genomes. This will enhance understanding regarding the potential role of CpG islands in epigenetic regulation.

Hemoporfin-Mediated Photodynamic Therapy for Port-Wine Stains on Extremities.

INTRODUCTION: Pulsed dye laser (PDL) is currently considered to be the first-line treatment for port-wine stains (PWSs) on the extremities despite its less than satisfactory therapeutic efficacy. Hemoporfin-mediated photodynamic therapy (HMME-PDT) is a vascular-targeted therapy that has rarely been used to treat PWSs on the extremities. Here, we evaluate the clinical efficacy and safety of HMME-PDT for the treatment of PWSs on the extremities. METHODS: Clinical data and dermoscopic images of PWSs on the extremities were obtained from 65 patients who underwent HMME-PDT between February 2019 and December 2022. The clinical efficacy of HMME-PDT was analyzed by comparing the pre- and post-treatment images. The safety of HMME-PDT was evaluated through observation during the treatment period and post-treatment follow-up. RESULTS: The efficacy rate of a single HMME-PDT session was 63.0% and that of two and three to six sessions was 86.7% and 91.3%, respectively. A positive correlation was found between therapeutic efficacy and the number of HMME-PDT sessions. The therapeutic efficacy of HMME-PDT was better on the proximal extremities than on other parts of the extremities (P = 0.038), and the efficacy of treating PWSs in each site was relatively improved with an increase of treatment time. The clinical efficacy of HMME-PDT differed across four PWS vascular patterns identified by dermoscopy (P = 0.019). However, there was no statistical difference in the therapeutic efficacy based on age, sex, type of PWS, and treatment history (P > 0.05), which may be partly attributed to the relatively small sample size or poor cooperation of infant patients. No obvious adverse reactions were observed during the follow-up period. CONCLUSIONS: HMME-PDT is a very safe and effective treatment for PWSs on the extremities. Multiple HMME-PDT treatments, lesions located in proximal limbs, and PWSs with type I and IV vascular patterns under dermoscopy were associated with higher efficacy of HMME-PDT. Dermoscopy may help predict the clinical efficacy of HMME-PDT. TRIAL REGISTRATION NO: 2020KJT085.

Alterations in gut microbiota and urine metabolomics in infants with yin-deficiency constitution aged 0-2 years.

Background: Based on the constitution theroy, infants are classified into balanced constitution (BC) and unbalanced constitution. Yin-deficiency constitution (YINDC) is a common type of unbalanced constitutions in Chinese infants. An infant's gut microbiota directly affects the child's health and has long-term effects on the maturation of the immune and endocrine systems throughout life. However, the gut microbiota of infants with YINDC remains unknown. Herein, we aimed to evaluate the intestinal flora profiles and urinary metabolites in infant with YINDC, find biomarkers to identify YINDC, and promote our understanding of infant constitution classification. Methods: Constitutional Medicine Questionnaires were used to assess the infants' constitution types. 47 infants with 21 cases of YINDC and 26 cases of BC were included, and a cross-sectional sampling of stool and urine was conducted. Fecal microbiota was characterized using 16S rRNA sequencing, and urinary metabolomics was profiled using UPLC-Q-TOF/MS method. YINDC markers with high accuracy were identified using receiver operating characteristic (ROC) analysis. Results: The diversity and composition of intestinal flora and urinary metabolites differed significantly between the YINDC and BC groups. A total of 13 obviously different genera and 55 altered metabolites were identified. Stool microbiome shifts were associated with urine metabolite changes. A combined marker comprising two genera may have a high potential to identify YINDC with an AUC of 0.845. Conclusions: Infants with YINDC had a unique gut microbiota and metabolomic profile resulting in a constitutional microclassification. The altered gut microbiome in YINDC may account for the higher risk of cardiovascular diseases. Metabolomic analysis of urine showed that metabolic pathways, including histidine metabolism, proximal tubule bicarbonate reclamation, arginine biosynthesis, and steroid hormone biosynthesis, were altered in infants with YINDC. Additionally, the combined bacterial biomarker had the ability to identify YINDC. Identifying YINDC in infancy and intervening at an early stage is crucial for preventing cardiovascular diseases.